MFAP5

Overview

MFAP5 (Microfibrillar-Associated Protein 5, also known as MAGP2) is an extracellular matrix glycoprotein associated with elastic microfibrils. In cancer, MFAP5 has emerged as a marker of cancer-associated fibroblast (CAF) subpopulations, particularly in contexts of mechanical stiffness-driven stromal activation. Its expression in the tumor microenvironment has been linked to pro-tumorigenic signaling via paracrine pathways.

Alterations observed in the corpus

  • MFAP5 co-expressed with SEMA7A, ACTA2, and COL1A1 in ACTA2+/MFAP5+ CAF subpopulations identified by scRNA-seq (OEP00001237, 13 GBC patients; 16 cell types); marks a myofibroblastic CAF subset in gallbladder cancer stroma PMID:24997986

Cancer types (linked)

  • GBC: MFAP5+ CAF subpopulation identified in scRNA-seq profiling of GBC tumor microenvironment; co-marks stiffness-activated fibroblasts alongside SEMA7A PMID:24997986

Co-occurrence and mutual exclusivity

  • Co-expressed with SEMA7A, ACTA2, COL1A1 in CAF subclusters in GBC scRNA-seq data; stiffness-driven CAF activation (16 kPa) upregulates this cluster of markers PMID:24997986

Therapeutic relevance

  • No direct therapeutic targeting reported. MFAP5+ CAF subpopulation is part of the SEMA7A-driven stromal axis; disrupting YAP1/TEAD1-mediated SEMA7A induction (e.g., with verteporfin) may indirectly affect this CAF population PMID:24997986

Open questions

  • Whether MFAP5 itself is functionally required for CAF-mediated tumor promotion, or is merely a co-expression marker, is not established.
  • External validation of MFAP5+ CAF prognostic significance in GBC beyond the single-institution cohort is needed.

Sources

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